ILAE POSITION PAPER

ILAE classification of the epilepsies: Position paper of the

ILAE Commission for Classification and Terminology
1,2,3
Ingrid E. Scheffer, 1Samuel Berkovic, 4Giuseppe Capovilla, 5Mary B. Connolly,
6
Jacqueline French, 7Laura Guilhoto, 8,9Edouard Hirsch, 10Satish Jain, 11Gary W. Mathern,
12
Solomon L. Mosh
e, 13Douglas R. Nordli, 14Emilio Perucca, 15Torbj
orn Tomson,
16
Samuel Wiebe, 17Yue-Hua Zhang, and 18,19Sameer M. Zuberi

Epilepsia, 58(4):512521, 2017

doi: 10.1111/epi.13709

Dr. Ingrid E. Scheffer
chairs the ILAE Task
Force on the
Classification of the
Epilepsies.
SUMMARY
The International League Against Epilepsy (ILAE) Classification of the Epilep-
sies has been updated to reflect our gain in understanding of the epilepsies
and their underlying mechanisms following the major scientific advances that
have taken place since the last ratified classification in 1989. As a critical tool
for the practicing clinician, epilepsy classification must be relevant and
dynamic to changes in thinking, yet robust and translatable to all areas of the
globe. Its primary purpose is for diagnosis of patients, but it is also critical for
epilepsy research, development of antiepileptic therapies, and communication
around the world. The new classification originates from a draft document
submitted for public comments in 2013, which was revised to incorporate
extensive feedback from the international epilepsy community over several
rounds of consultation. It presents three levels, starting with seizure type,
where it assumes that the patient is having epileptic seizures as defined by
the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type,
the next step is diagnosis of epilepsy type, including focal epilepsy, generalized
epilepsy, combined generalized, and focal epilepsy, and also an unknown epi-
lepsy group. The third level is that of epilepsy syndrome, where a specific syn-
dromic diagnosis can be made. The new classification incorporates etiology
along each stage, emphasizing the need to consider etiology at each step of
diagnosis, as it often carries significant treatment implications. Etiology is bro-
ken into six subgroups, selected because of their potential therapeutic conse-
quences. New terminology is introduced such as developmental and epileptic
encephalopathy. The term benign is replaced by the terms self-limited and

Accepted January 21, 2017; Early View publication March 8, 2017.

1
Department of Medicine, The University of Melbourne, Austin Health, Melbourne, Victoria, Australia; 2Department of Paediatrics, Royal Childrens
Hospital, The University of Melbourne, Melbourne, Victoria, Australia; 3Florey Institute, Melbourne, Victoria, Australia; 4Child Neuropsychiatry
Department, Epilepsy Center, C. Poma Hospital, Mantova, Italy; 5Department of Pediatrics, British Columbias Childrens Hospital, University of British
Columbia, Vancouver, British Columbia, Canada; 6Department of Neurology, NYU School of Medicine, New York, New York, U.S.A.; 7Department of
Neurology, Federal University of S~ao Paulo; University Hospital, University of S~ao Paulo, S~ao Paulo, Brazil; 8University Hospital INSERM U 964,

Lyon, France; 10Indian Epilepsy Centre, New Delhi, India; 11Departments of Neurosurgery, Psychiatry and Biobehavioral
Strasbourg, France; 9IDEE,
Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, U.S.A.; 12Saul R. Korey Department of Neurology, Dominick P. Purpura
Department of Neuroscience and Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York,
U.S.A.; 13Division of Neurology, Childrens Hospital Los Angeles, Los Angeles, California, U.S.A.; 14C. Mondino National Neurological Institute and
Clinical Pharmacology Unit, University of Pavia, Pavia, Italy; 15Department of Clinical Neuroscience, Karolinska Institute, Stockholm,
Sweden; 16Departments of Clinical Neurosciences and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 17Department of
Pediatrics, Peking University First Hospital, Beijing, China; 18Paediatric Neurosciences Research Group, Fraser of Allander Neurosciences Unit, Royal
Hospital for Children, Glasgow, United Kingdom; and 19School of Medicine, University of Glasgow, Glasgow, United Kingdom
Address correspondence to Ingrid E. Scheffer, Epilepsy Research Centre, 245 Burgundy St, Heidelberg, Vic. 3084, Australia. E-mail:
scheffer@unimelb.edu.au
Wiley Periodicals, Inc.
2017 International League Against Epilepsy

512

pharmacoresponsive, to be used where appropriate. It is hoped that this new
framework will assist in improving epilepsy care and research in the 21st
century.
KEY WORDS: Classification, Epilepsy syndromes, Terminology, Etiology.
Key Points
The ILAE presents a revised framework for the Classi-
fication of the Epilepsies, designed to work with the
classification of seizure types
Levels of diagnosis: seizure type, epilepsy type (focal,
generalized, combined generalized and focal,
unknown) and epilepsy syndrome
An etiologic diagnosis should be considered from
when the patient first presents, and at each step along
the diagnostic pathway; a patients epilepsy may be
classified into more than one etiological category
The term benign is replaced by the terms self-lim-
ited and pharmacoresponsive to be used where
appropriate
The term developmental and epileptic encephalopa-
thy can be applied in whole or in part where
appropriate
Ongoing efforts to refine the classification of the epilep-
sies have been made by the International League Against
Epilepsy (ILAE) almost since its inception in 1909 and
gained special momentum in the early 1960s when new con-
cepts of classification were proposed by Henri Gastaut.13
Intense debate and acquisition of new knowledge in the next
two decades led to the landmark 1985 ILAE Classification
of Epilepsies and Epileptic Syndromes,4 which was soon
followed by a revised version ratified by the ILAE General
Assembly in 1989.5 The 1989 Classification has been highly
influential worldwide and has had a major impact on epi-
lepsy care and research. The work presented herein builds
on the efforts of many over more than a century; we
acknowledge their seminal contributions in the develop-
ment of the classification of the epilepsies.
Although many concepts outlined in the 1989 ILAE clas-
sification remain valid to this day, it has become increas-
ingly clear that a revision is needed to account for
subsequent scientific discoveries that over the last few dec-
ades have fundamentally changed our understanding of the
epilepsies as well as our approach to the diagnosis and man-
agement of individuals with epilepsy.
Epilepsy classification is the key clinical tool in evaluat-
ing an individual who is presenting with seizures. It influ-
ences every clinical consultation yet its impact stretches far
513
Classification of the Epilepsies
beyond the clinical domain to clinical and basic epilepsy
research and to the development of novel therapies. Classifi-
cation serves many purposes: providing a framework for
understanding the type of seizures that the patient has, the
other seizure types that are more likely to occur in that indi-
vidual, the potential triggers for their seizures, and often
their prognosis. Classification also informs the risks of
comorbidities including learning difficulties, intellectual
disability, psychiatric features such as autism spectrum dis-
order, and mortality risk such as sudden unexpected death in
epilepsy (SUDEP). It is notable that classification often
guides the selection of antiepileptic therapies.
Classification of the epilepsies has evolved dramatically
since its inception in the 1960s.69 The many iterations in
classification reflect advances in understanding phenotypic
patterns and underlying mechanisms, based on major contri-
butions from clinical and basic research from around the
world. These insights are incorporated into the many facets
of clinical care for patients and lead to progress in the devel-
opment of innovative treatments, be they pharmacologic or
dietary therapies, surgical approaches or device develop-
ment. Classification will always be a dynamic process, iter-
ative to the new insights gained through research and
improved understanding of this heterogeneous group of dis-
eases. Its continued evolution into the future promises to
lead to further advances in patient care.
Classification engenders passionate debate. This is partly
because it is built on the complex clinical constructs under-
pinning epilepsy diagnosis and partly because it is so critical
to our daily practice. Classification has been based on expert
opinion drawing together epileptologists and related experts
from around the world. Although there is no doubt that the
desired endpoint is a scientifically based classification, our
understanding is not sufficiently advanced to construct a
classification on a scientifically rigorous basis.9 Thus cur-
rent proposals are based on a combination of the latest sci-
entific understanding coupled with high-level expert
opinion, including an extensive consultation with epilepsy
professionals and the wider epilepsy community
worldwide.
When a patient presents with seizures, the clinician works
through several critical steps in making a diagnosis. Before
attempting to classify a seizure, the physician must deter-
mine whether the paroxysmal event is indeed an epileptic
seizure with a myriad of differential diagnoses being possi-
ble. These include convulsive syncope, parasomnias, move-
ment disorders, and other nonepileptic events (https://
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
514
I. E. Scheffer et al.
www.epilepsydiagnosis.org/epilepsy-imitators.html). This
diagnostic step is taken as already established at the point of
beginning to classify the patients epilepsy.
In terms of epilepsy classification, the clinician starts by
classifying the type of seizure. This is the subject of the
companion paper on the new classification of seizure
types.10 Then, the patients type of epilepsy needs to be clas-
sified and, in many cases, a specific epilepsy syndrome diag-
nosis can be made. Just as importantly, strenuous attempts
to identify the etiology of the patients epilepsy should be
made at each step in the diagnostic pathway. Classification
of seizure type and epilepsy type both take into account the
results of investigations such as electroencephalography
(EEG) and neuroimaging studies together with other studies
exploring the underlying etiology of the epilepsy. Herein,
we present the first major Classification of the Epilepsies
since the last ratified ILAE Classification in 1989.
Methods
In the past, ILAE position papers on fundamental matters
such terminology, definition, and classification of seizures
and epilepsy required ratification by the General Assembly
through a vote by the representatives of the ILAE Chapters
from around the world.5 This approach is no longer optimal,
since it does not permit adequate engagement of the greatly
expanded constituency of epilepsy experts around the world
and fails to exploit opportunities offered by impressive
advances in communication tools.
Consequently, in 2013, the League set in place a new pro-
cess for the finalization and approval of position documents,
that is, documents that reflect the ILAE position on topics
that involve adoption of a common language or set of defini-
tions (e.g., defining epilepsy, classification).11 This process
is highly iterative and involves initial production of the doc-
ument by a group of experts selected by the League, posting
the document on the ILAE website, soliciting comments
and criticism by all stakeholders, and appointing a separate
expert panel to review and incorporate the public comments.
This process takes place in parallel with the peer review
conducted by the journal to which the document is submit-
ted for publication (http://www.ilae.org/Visitors/Docume
nts/Guideline-PublPolicy-2013Aug.pdf).
In the case of the revised Classification, a first proposal
that preceded implementation of the procedure outlined
above was published by the ILAE Commission on Classifi-
cation and Terminology in 2010.9 The emphasis was on
employing transparent terminology, where words mean
what they say. The 2010 publication triggered extensive dis-
cussion and commentaries.1229 A new Commission on
Classification and Terminology was subsequently
appointed by the ILAE Executive and tasked to produce a
revised Classification through the procedure outlined for
ILAE position documents. The Commission submitted the
initial document in 2013, and the document was posted
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
online inviting discussion (Supporting Information for Sch-
effer et al.30). Avid community engagement and debate
occurred, with 128 comments received from 43 countries.
The response was so extensive and the feedback on impor-
tant concepts so conflicting that the panel in charge of
reviewing the public comments determined that further
pubic engagement was necessary to ensure the highest pos-
sible level of agreement. The roadmap followed by the
panel to solicit further engagement and to respond to feed-
back from stakeholders is described in an article published
in Epilepsia Open in 2016, which again invited feedback
from the global community.30 Further comments and opin-
ions were then deliberated and considered in finalizing the
present position document which defines the Classification
of the Epilepsies in 2017.
Classification of the Epilepsies
The new Classification of the Epilepsies is a multilevel
classification, designed to cater to classifying epilepsy in
different clinical environments (Fig. 1). This is in acknowl-
edgement of the wide variation in resources around the
world, meaning that different levels of classification will be
possible depending on the resources available to the clini-
cian making the diagnosis. Where possible, a diagnosis at
all three levels should be sought as well as the etiology of
the individuals epilepsy.
Seizure type
The starting point of the Epilepsy classification frame-
work is the Seizure Type; it assumes that the clinician has
already made a definite diagnosis of an epileptic seizure and
is not meant to be a diagnostic algorithm to distinguish
epileptic from nonepileptic events. The Seizure Type Clas-
sification is determined according to the new nomenclature
in the accompanying paper.10 Seizures are classified into
focal onset, generalized onset, and unknown onset.
In some settings, classification according to Seizure Type
may be the maximum level possible for diagnosis as there
may be no access to EEG, video. and imaging studies. In
other cases, there may simply be too little information avail-
able to be able to make a higher level diagnosis, such as
when a patient has only had a single seizure.
Epilepsy type
The second level is that of Epilepsy Type and assumes
that the patient has a diagnosis of epilepsy based on the
2014 definition.31 The Epilepsy Type level includes a new
category of Combined Generalized and Focal Epilepsy in
addition to the well-established Generalized Epilepsy
and Focal Epilepsies. It also includes an Unknown cate-
gory. Many epilepsies will include multiple types of
seizures.
For a diagnosis of Generalized Epilepsy, the patient
would typically show generalized spike-wave activity on

Figure 1.
Framework for classification of the
epilepsies. *Denotes onset of seizure.
Epilepsia ILAE
EEG. Individuals with generalized epilepsies may have a
range of seizure types including absence, myoclonic, atonic,
tonic, and tonicclonic seizures. The diagnosis of general-
ized epilepsy is made on clinical grounds, supported by the
finding of typical interictal EEG discharges. Caution needs
to be exercised for a patient with generalized tonicclonic
seizures and a normal EEG. In this case, supportive evi-
dence would need to be present to make a diagnosis of gen-
eralized epilepsy, such as myoclonic jerks or a relevant
family history.
Focal Epilepsies include unifocal and multifocal disor-
ders as well as seizures involving one hemisphere. A range
of seizure types can be seen including focal aware seizures,
focal impaired awareness seizures, focal motor seizures,
focal non-motor seizures, and focal to bilateral tonicclonic
seizures. The interictal EEG typically shows focal epilepti-
form discharges, but the diagnosis is made on clinical
grounds, supported by EEG findings.
The new group of Combined Generalized and Focal
Epilepsies exists, as there are patients who have both gener-
alized and focal seizures. The diagnosis is made on clinical
grounds, supported by EEG findings. Ictal recordings are
helpful but not essential. The interictal EEG may show both
generalized spike-wave and focal epileptiform discharges,
but epileptiform activity is not required for the diagnosis.
Common examples in which both types of seizures occur
are Dravet syndrome and Lennox-Gastaut syndrome.
The Epilepsy type may also be the final level of diagnosis
achievable where the clinician is unable to make an Epi-
lepsy Syndrome diagnosis. Examples include the following:
the common situation of a child or adult with nonlesional
temporal lobe epilepsy who has Focal Epilepsy with no
known etiology; a 5-year-old child presenting with general-
ized tonicclonic seizures and generalized spike-wave
515
Classification of the Epilepsies
activity on EEG who cannot be classified into a known epi-
lepsy syndrome but has a clear-cut diagnosis of Generalized
Epilepsy; or the less common scenario of a 20-year-old
woman with both focal impaired awareness seizures
and absence seizures with both focal discharges and gener-
alized spike wave on EEG recordings and normal MRI, who
would therefore have a diagnosis of Combined Generalized
and Focal Epilepsy.
The term Unknown is used to denote where it is
understood that the patient has Epilepsy but the clinician
is unable to determine if the Epilepsy Type is focal or gen-
eralized because there is insufficient information avail-
able. This may be for a variety of reasons. There may be
no access to EEG, or the EEG studies may have been
uninformative, for example, normal. If the Seizure Type(s)
are unknown, then the Epilepsy Type may be unknown for
similar reasons, although the two may not always be
concordant. For example, the patient may have had sev-
eral symmetrical tonicclonic seizures without focal fea-
tures and normal EEG recordings. Thus the onset of the
seizures is unknown and the person has an unknown
epilepsy type.
Epilepsy syndrome
The third level is an Epilepsy Syndrome diagnosis. An
epilepsy syndrome refers to a cluster of features incorporat-
ing seizure types, EEG, and imaging features that tend to
occur together. It often has age-dependent features such as
age at onset and remission (where applicable), seizure trig-
gers, diurnal variation, and sometimes prognosis.4,5 It may
also have distinctive comorbidities such as intellectual and
psychiatric dysfunction, together with specific findings on
EEG and imaging studies. It may have associated etiologic,
prognostic, and treatment implications. It is important to
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doi: 10.1111/epi.13709
516
I. E. Scheffer et al.
note that an epilepsy syndrome does not have a one-to-one
correlation with an etiologic diagnosis and serves a different
purpose such as guiding management. There are many well-
recognized syndromes, such as childhood absence epilepsy,
West syndrome, and Dravet syndrome, although it should
be noted that there has never been a formal classification of
syndromes by the ILAE.9 The recently developed educa-
tional ILAE website, epilepsydiagnosis.org, provides an
excellent resource to understand the parameters for diagno-
sis, review videos of seizure types and the EEG features of
many established syndromes, and has been devised as a
teaching tool.
Idiopathic Generalized Epilepsies
Within the Generalized Epilepsies is the well-recognized
and common subgroup of the Idiopathic Generalized
Epilepsies (IGEs). The IGEs encompass four well-estab-
lished epilepsy syndromes: Childhood Absence Epilepsy,
Juvenile Absence Epilepsy, Juvenile Myoclonic Epilepsy
and Generalized TonicClonic Seizures Alone (formerly
known as Generalized TonicClonic Seizures on Awaken-
ing but modified in recognition that seizures can occur at
any time of day). The intention to remove the term idio-
pathic from the nomenclature of Epilepsy Classification
was suggested, as its definition was no known or suspected
etiology other than possible hereditary predisposition.4
The Greek term idios refers to self, own, and personal,
and is thus meant to reflect the genetic etiology without
explicitly saying so. Idiopathic may therefore be regarded
as an imprecise term given our increasing recognition and
discovery of the genes involved in many epilepsies, includ-
ing those with monogenic (with inherited or de novo patho-
genic variants) or complex (polygenic with or without
environmental factors) inheritance. In addition, the word
genetic may sometimes be wrongly interpreted as synony-
mous with inherited.
It is therefore more meaningful to refer to this group of
syndromes as Genetic Generalized Epilepsies (GGEs),
where the clinician feels there is sufficient evidence for this
classification. Such evidence is drawn from meticulous clin-
ical research of the inheritance of these syndromes in twin
and family studies and does not mean that specific genetic
mutations have been identified. Indeed, it is currently rarely
the case that the genetic mutation(s) causing a patients epi-
lepsy has been determined, perhaps with the exception of
the infantile onset developmental and epileptic encephalo-
pathies, where many patients have been shown to have a de
novo pathogenic variant.32
There has been, however, considerable desire to retain
the term IGE. The Task Force has therefore decided that the
term IGE will be acceptable specifically for the group of
four epilepsy syndromes: Childhood Absence Epilepsy,
Juvenile Absence Epilepsy, Juvenile Myoclonic Epilepsy,
and Generalized TonicClonic Seizures Alone. In individ-
ual cases, the term Genetic Generalized Epilepsy may be
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
used where the clinician is comfortable with invoking a
genetic etiology.
Self-limited focal epilepsies
There are several self-limited focal epilepsies, typically
beginning in childhood. The most common is self-limited
epilepsy with centrotemporal spikes, formerly called be-
nign epilepsy with centrotemporal spikes. Others included
in this broad group are the self-limited occipital epilepsies
of childhood, with the early-onset form described by
Panayiotopoulos and the late-onset form by Gastaut.33
Other self-limited frontal lobe,34 temporal35, and parietal
lobe epilepsies36 have been described with some beginning
in adolescence and even adult life.
Etiology
From the moment that the patient presents with a first
epileptic seizure, the clinician should be aiming to deter-
mine the etiology of the patients epilepsy. A range of etio-
logic groups has been recognized, with emphasis on those
that have implications for treatment. Often the first investi-
gation carried out involves neuroimaging, ideally MRI
where available. This enables the clinician to decide if there
is a structural etiology for the patients epilepsy. The five
additional etiologic groups are genetic, infectious, meta-
bolic, and immune, as well as an unknown group (Fig. 1). A
patients epilepsy may be classified into more than one etio-
logic category; the etiologies are not hierarchical, and the
importance given to the patients etiological group may
depend on the circumstance. For instance, a patient with
tuberous sclerosis has both a structural and a genetic etiol-
ogy; the structural etiology is critical for epilepsy surgery,
whereas the genetic etiology is key for genetic counseling
and consideration of novel therapies such as mammalian
target of rapamycin (mTOR) inhibitors.
Structural etiology
The concept behind a structural etiology is that a struc-
tural abnormality has a substantially increased risk of being
associated with epilepsy based on appropriately designed
studies.9 A structural etiology refers to abnormalities visible
on structural neuroimaging where the electroclinical assess-
ment together with the imaging findings lead to a reasonable
inference that the imaging abnormality is the likely cause of
the patients seizures. Structural etiologies may be acquired
such as stroke, trauma, and infection, or genetic such as
many malformations of cortical development. Despite there
being a genetic basis with such malformations, the structural
correlate underpins the persons epilepsy. Identification of a
subtle structural lesion requires appropriate MRI studies
using specific epilepsy protocols.37
There are well-recognized associations within the epilep-
sies with a structural etiology. These include the relatively
frequent finding of mesial temporal lobe seizures with hip-
pocampal sclerosis. Other key associations include gelastic

seizures with hypothalamic hamartoma, Rasmussen syn-
drome, and hemiconvulsion-hemiplegia-epilepsy. Recogni-
tion of these associations is important to ensure that the
patients imaging is carefully examined for a specific struc-
tural abnormality. This in turn highlights the need for con-
sideration for epilepsy surgery should the patient fail
medical therapy.
The underlying basis for a structural abnormality may be
genetic or acquired, or both. For example, polymicrogyria
may be secondary to mutations in genes such as GPR56, or
acquired, secondary to intrauterine cytomegalovirus infec-
tion.38 Acquired structural causes include hypoxic-ischemic
encephalopathy, trauma, infection, and stroke. Where a
structural etiology has a well-defined genetic basis such as
tuberous sclerosis complex, which is caused by mutations in
the genes TSC1 and TSC2 encoding hamartin and tuberin,
respectively, both etiologic terms, structural and genetic can
be used.
Genetic etiology
The concept of a genetic epilepsy is that it results directly
from a known or presumed genetic mutation in which sei-
zures are a core symptom of the disorder. The epilepsies in
which a genetic etiology has been implicated are quite
diverse and, in most cases, the underlying genes are not yet
known.
First, the inference of a genetic etiology may be based
solely on a family history of an autosomal dominant disor-
der. For example, in the syndrome of Benign Familial
Neonatal Epilepsy, most families have mutations of one of
the potassium channel genes, KCNQ2 or KCNQ3.39 Con-
versely, in the syndrome of Autosomal Dominant Nocturnal
Frontal Lobe epilepsy, the underlying mutation is known in
only a small proportion of individuals at this time.40
Second, a genetic etiology may be suggested by clinical
research in populations with the same syndrome such as
Childhood Absence Epilepsy or Juvenile Myoclonic Epi-
lepsy. Evidence for a genetic basis comes from elegant stud-
ies such as Lennoxs twin studies in the 1950s and familial
aggregation studies.41,42
Third, a molecular basis may have been identified and
may implicate a single gene or copy number variant of
major effect. There is an increasing number of patients with
known genetic abnormalities causing both severe and mild
epilepsies. Molecular genetics has led to identification of
the causative mutation in a large number of epilepsy genes,
most frequently arising de novo, in 3050% of infants with
severe developmental and epileptic encephalopathies.32
The best known example is Dravet syndrome in which
>80% of patients have a pathogenic variant of SCN1A. It is
notable that a monogenic etiology may cause a spectrum of
mild to severe epilepsies, such as SCN1A mutations, which
are associated with Dravet syndrome and Genetic Epilepsy
with Febrile Seizures Plus (GEFS+), and may have implica-
tions for treatment.43,44 Understanding the phenotypic
517
Classification of the Epilepsies
spectrum associated with mutations of a specific gene is
critical information, as the finding of a mutation in a speci-
fic gene may not, on its own, enable prediction of the out-
come. Interpretation of its significance needs to be
considered in the context of the electroclinical presentation.
Thus, to date, the majority of genes show phenotypic hetero-
geneity and the majority of syndromes reveal genetic
heterogeneity.
Where epilepsy follows complex inheritance, which
implies multiple genes with/without an environmental con-
tribution, susceptibility variants may be identified that con-
tribute to causation but are insufficient alone to cause
epilepsy.45,46 In this setting, there may be no family history
of seizures because other family members do not have
enough epilepsy genetic variants to be affected.
It is important to note that genetic does not equate with
inherited. An increasing number of de novo mutations are
being identified in both severe and mild epilepsies.4752
This means that the patient has a new mutation that has
arisen in him or her, and therefore is unlikely to have a fam-
ily history of seizures and has not inherited the genetic
mutation. Nevertheless, this patient may now have a herita-
ble form of epilepsy. For example if the individual has a de
novo dominant mutation, their offspring will have a 50%
risk of inheriting the mutation. This does not necessarily
mean that their children will have epilepsy, as its expression
will depend on the penetrance of the mutation.
Drilling down further, patients may be mosaic for a muta-
tion. This means they have two populations of cells, with
one population having the mutation and the other having the
wild-type (normal) allele. Mosaicism may affect the severity
of their epilepsy, with lower mosaicism rates resulting in a
milder severity of epilepsy, as shown in SCN1A studies.53
A genetic etiology does not exclude an environmental
contribution. It is well accepted that environmental factors
contribute to seizure disorders; for example, many individu-
als with epilepsy are more likely to have seizures with sleep
deprivation, stress, and illness. A genetic etiology refers to a
pathogenic variant (mutation) of significant effect in caus-
ing the individuals epilepsy.
Infectious etiology
The most common etiology worldwide is where epilepsy
occurs as a result of an infection.54 The concept of an infec-
tious etiology is that it directly results from a known infec-
tion in which seizures are a core symptom of the disorder.
An infectious etiology refers to a patient with epilepsy,
rather than with seizures occurring in the setting of acute
infection such as meningitis or encephalitis. Common
examples in specific regions of the world include neurocys-
ticercosis, tuberculosis, HIV, cerebral malaria, subacute
sclerosing panencephalitis, cerebral toxoplasmosis, and
congenital infections such as Zika virus and cytomegalo-
virus. These infections sometimes have a structural corre-
late. An infectious etiology carries specific treatment
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doi: 10.1111/epi.13709
518
I. E. Scheffer et al.
implications. An infectious etiology may also refer to the
postinfectious development of epilepsy, such as viral
encephalitis leading to seizures in the aftermath of the acute
infection.
Metabolic etiology
A range of metabolic disorders is associated with epi-
lepsy. This area is expanding and a greater understanding of
the phenotypic spectrum emerging. The concept of a meta-
bolic epilepsy is that it results directly from a known or pre-
sumed metabolic disorder in which seizures are a core
symptom of the disorder. Metabolic causes refer to a well-
delineated metabolic defect with manifestations or bio-
chemical changes throughout the body such as porphyria,
uremia, aminoacidopathies, or pyridoxine-dependent sei-
zures. In many cases, metabolic disorders will have a
genetic defect. It is likely that most metabolic epilepsies will
have a genetic basis, but some may be acquired such as cere-
bral folate deficiency. The identification of specific meta-
bolic causes of epilepsy is extremely important due to
implications for specific therapies and potential prevention
of intellectual impairment.
Immune etiology
The concept of an immune epilepsy is that it results
directly from an immune disorder in which seizures are a
core symptom of the disorder. A range of immune epilepsies
has been recently recognized with characteristic presenta-
tions in both adults and children.54 An immune etiology can
be conceptualized as where there is evidence of autoim-
mune-mediated central nervous system inflammation. Diag-
nosis of these autoimmune encephalitides is rapidly
increasing, particularly with greater access to antibody test-
ing. Examples include anti-NMDA (N-methyl-D-aspartate)
receptor encephalitis and anti-LGI1 encephalitis.55 With the
emergence of these entities, this etiologic subgroup
deserves a specific category, particularly given the treat-
ment implications with targeted immunotherapies.
Unknown etiology
Unknown means that the cause of the epilepsy is not yet
known. There remain many patients with epilepsy for whom
the cause is not known. In this category it is not possible to
make a specific diagnosis apart from the basic electroclini-
cal semiology such as frontal lobe epilepsy. The extent to
which a cause can be found depends on the extent of the
evaluation available to the patient. This differs across differ-
ent health care settings and countries and hopefully will
improve over time in resource-poor countries.
Comorbidities
There is increasing awareness that many of the epilepsies
are associated with comorbidities such as learning, psycho-
logical, and behavioral problems (Fig. 1, left hand vertical
oval). These range in type and severity, from subtle learning
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
difficulties to intellectual disability, to psychiatric features
such as autism spectrum disorders and depression, to psy-
chosocial concerns. In the more severe epilepsies, a com-
plex range of comorbidities may be seen, including motor
deficits such as cerebral palsy or deterioration in gait, move-
ment disorders, scoliosis, sleep, and gastrointestinal disor-
ders. Like etiology, it is important that the presence of
comorbidities be considered for every patient with epilepsy
at each stage of classification, enabling early identification,
diagnosis, and appropriate management.
New Terminology and
Definitions
Developmental and epileptic encephalopathies
The term epileptic encephalopathy was redefined in the
Berg et al.9 report as where the epileptic activity itself con-
tributes to severe cognitive and behavioral impairments
above and beyond what might be expected from the under-
lying pathology alone (e.g., cortical malformation). Global
or selective impairments can worsen over time. These
impairments can be seen along a spectrum of severity and
across all epilepsies, and can occur at any age.
The concept of the epileptic encephalopathy may be
applicable to epilepsies at all ages and should be utilized
more widely than just for the severe epilepsies with onset in
infancy and childhood. Many epilepsy syndromes associ-
ated with encephalopathy have a genetic etiology, such as
West syndrome, where there is marked genetic heterogene-
ity, and Epileptic encephalopathy with continuous spike-
and-wave during sleep (CSWS), where the first genes have
begun to emerge.32 Equally, such syndromes may have an
acquired cause such as hypoxic-ischemic encephalopathy or
stroke, or may be associated with a malformation of cortical
development that may also have a genetic or acquired etiol-
ogy.
The concept of an epileptic encephalopathy can also be
applied to single gene disorders, such as CDKL5
encephalopathy and CHD2 encephalopathy. However, a
single gene may cause an epileptic encephalopathy in some
individuals and a self-limited epilepsy in others; examples
include SCN1A, SCN2A, SLC2A1, KCNQ2, KCNA2, and
CHD2. In an epileptic encephalopathy, the abundant epilep-
tiform activity interferes with development resulting in cog-
nitive slowing and often regression, and sometimes is
associated with psychiatric and behavioral consequences.
The epileptiform activity can cause regression in an individ-
ual with normal development or preexisting developmental
delay, who then shows developmental plateauing or regres-
sion. A key component of the concept is that amelioration of
the epileptiform activity may have the potential to improve
the developmental consequences of the disorder. This is a
critical issue from a clinical perspective and one often mir-
rored in the observations of families and clinicians.

Many of these severe genetic disorders also have devel-
opmental consequences arising directly from the effect of
the genetic mutation, in addition to the effect of the frequent
epileptic activity on development. There are several ways in
which this may manifest. There may be preexisting develop-
mental delay, complicated by plateauing or regression with
seizure onset or with prolonged seizures. In other disorders,
developmental slowing may occur on a background of nor-
mal development, with the slowing emerging prior to the
presence of frequent epileptic activity on EEG. A well-
known example is the relatively common encephalopathy
of Dravet syndrome, in which developmental slowing or
regression occurs between 1 and 2 years of age, at a time
when epileptiform activity on EEG is typically not yet fre-
quent. This suggests a developmental component in addi-
tion to an epileptic component, with both occurring
secondary to the underlying sodium channel subunit gene
(SCN1A) mutation found in >80% of cases. In a third group,
the epilepsy may settle down relatively early in the childs
history, but the developmental consequences may remain
profound as seen in some patients with KCNQ2
encephalopathy or STXBP1 encephalopathy. These obser-
vations, pertinent to many of the genetic encephalopathies,
suggest that a broadening of the terminology, where appro-
priate, to include the word developmental, acknowledges
that both aspects may be playing a role in the clinical pre-
sentation. These concepts are crucial to understanding the
disease process for both families and clinicians.
It is therefore suggested that the term developmental
and epileptic encephalopathy be used where appropriate
and can be applied to individuals of any age. This allows for
the use of either or both descriptors: developmental
encephalopathy where there is just developmental impair-
ment without frequent epileptic activity associated with
regression or further slowing of development; epileptic
encephalopathy where there is no preexisting developmen-
tal delay and the genetic mutation is not thought to cause
slowing in its own right; and developmental and epileptic
encephalopathy where both factors play a role. Often it may
not be possible to disentangle whether the epileptic or devel-
opmental component is more important in contributing to a
patients presentation.
Many patients with these disorders have been classified
previously as having symptomatic generalized epilepsies;
however, this term will no longer be used as it was applied
to a highly heterogeneous group of patients. This term has
been applied to patients with developmental encephalopa-
thies and epilepsy (e.g., static intellectual disability and
mild epilepsy), those with epileptic encephalopathies, those
with developmental and epileptic encephalopathies, as well
as some patients with generalized epilepsy or combined
generalized and focal epilepsy. The new classification will
allow more precise classification of these individuals
epilepsy.
519
Classification of the Epilepsies
In many instances where a genetic mutation of major
effect is identified, the terms developmental and epileptic
encephalopathy may be subsumed by using the name of the
underlying condition. For example, many of the well-recog-
nized developmental and epileptic encephalopathies can
now be called by their gene name together with the word
encephalopathy, such as STXBP1 encephalopathy or
KCNQ2 encephalopathy. This is particularly important
when referring to a genetic disease where genes are associ-
ated with both severe and self-limited, pharmacoresponsive
epilepsies, such as KCNQ2 or SCN2A. Then the term
encephalopathy can be used to denote the severe form of
the disease associated with developmental impairment.
Self-limited and pharmacoresponsive
With increasing recognition of the impact of these comor-
bidities on an individuals life, there has been considerable
concern that the term benign underestimates this burden,
particularly in the milder epilepsy syndromes such as
benign epilepsy with centrotemporal spikes (BECTS) and
childhood absence epilepsy (CAE). Despite the gestalt of a
benign syndrome, BECTS may be associated with transient
or long-lasting cognitive effects56,57 and CAE with signifi-
cant psychosocial consequences such as increased risk of
early pregnancy.58
The Berg et al. report9 suggested new terms to distill the
elements implied in the term benign. Thus benign, as a
descriptor for epilepsy, is replaced by both self-limited
and pharmacoresponsive, each replacing different com-
ponents of the meaning of benign. Self-limited refers to
the likely spontaneous resolution of a syndrome. Pharma-
coresponsive means that the epilepsy syndrome will be
likely to be controlled with appropriate antiepileptic ther-
apy. It is important to acknowledge, however, that there will
be individuals with these syndromes who are not pharma-
coresponsive. As noted previously, there is no formal ILAE
classification of syndromes; however, we expect the word
benign in time will be replaced in the names of specific syn-
dromes. The terms malignant and catastrophic will no
longer be used; they will be removed from the epilepsy lexi-
con because of their serious and devastating connotations.
It is hoped that this new Classification of the Epilepsies
will serve the epilepsy community well, leading to
improved diagnosis, understanding of etiology, and targeted
therapies to the patients disease. It is notable that even
where the etiology is clearly defined, the underlying mecha-
nism producing recurrent seizures still requires elucidation.
With significant advances in understanding the neurobiol-
ogy of seizures and epileptic diseases, there have been
major paradigm shifts in the concepts underpinning classifi-
cation. This Classification is designed to mirror current
understanding, so that it is relevant to clinical practice as the
preeminent tool for communication in both clinical and
research domains.
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
520
I. E. Scheffer et al.
Disclosure of Conflict of
Interest
Ingrid Scheffer received support from and/or has served as a paid con-
sultant for UCB, Eisai, Athena Diagnostics, GlaxoSmithKline, Transge-
nomics, and Biocodex. She serves on the editorial boards of Neurology
and Epileptic Disorders. She has received grants from the National
Health and Medical Research Council, Australian Research Council,
National Institutes of Health (NIH), Human Research Council, Citizens
United for Research in Epilepsy (CURE), the US Department of Defense,
and the March of Dimes. Samuel Berkovic discloses payments from
UCB Pharma, Novartis Pharmaceuticals, Sanofi-Aventis, and Jansen
Cilag for advisory board and educational activities, and a patent for
SCN1A testing held by Bionomics Inc licensed to various diagnostic
companies. Giuseppe Capovilla serves on the editorial board of the Euro-
pean Journal of Pediatric Neurology. Mary Connolly has received
research grants and/or speakers honoraria from UCB, Novartis, Biocodex,
Eisai, and Sage Therapeutics. All honoraria are donated to the Epilepsy
Research and Development Fund. She has also received research grants
from CIHR (Canadian Institute for Health Research) and The Alva Foun-
dation. She is Co-Chair of the Canadian Paediatric Epilepsy Network.
Jacqueline French: The Epilepsy Study Consortium pays her university
employer for her consultant time related to Acorda, Anavex, Brabant
Pharma, Bio-Pharm Solutions, Eisai Medical Research, GlaxoSmithK-
line, GW Pharma, Impax, Johnson & Johnson, Marinus, Neusentis,
Novartis, Roivant, Pfizer, Sage, Sunovion, SK Life Sciences, Supernus
Pharmaceuticals, Takeda, UCB, Upsher-Smith, Ultragenyx, Vertex,
Zogenix, Zynerba, and the Scientific Advisory Board for Anavex, UCB;
grants and research from Acorda, Alexza, LCGH, Eisai Medical
Research, Lundbeck, Pfizer, SK Life Sciences, UCB, Upsher-Smith, and
Vertex; and grants from National Institute of Neurological Disorders and
Stroke, Epilepsy Therapy Project, Epilepsy Research Foundation, Epi-
lepsy Study Consortium. She is on the editorial board of Lancet Neurol-
ogy, Neurology Today, and Epileptic Disorders, and is an Associate
Editor of Epilepsia, for which she receives a fee. Laura Guilhoto: serves
on the editorial board of SeizureEuropean Journal of Epilepsy.
Edouard Hirsch has received support from UCB, and/or has served as a
paid consultant for UCB, Eisai, and Bial. Satish Jain and Yue-Hua Zhang
have no disclosures. Gary Mathern is partially supported by the Davies/
Crandall Chair for Epilepsy Research at UCLA and is co-editor in chief
for Epilepsia and Epilepsia Open. He is also on the editorial board of
Neurology, and the Data Management Committee for NeuroPace, Inc.
Solomon L. Mosh
e MD is the Charles Frost Chair in Neurosurgery and
Neurology and funded by grants from NIH NS43209 and
1U54NS100064-01, CURE Infantile Spasms Initiative, the US Depart-
ment of Defense (W81XWH-13-1-0180), the Heffer Family and the
Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and
Laurie Marsh/Dan Levitz families. He serves as Associate Editor of Neu-
robiology of Disease, and is on the editorial boards of Brain and Devel-
opment, Pediatric Neurology, and Physiological Research. He receives
from Elsevier an annual compensation for his work as Associate Editor
of Neurobiology of Disease and royalties from two books he co-edited.
He received a consultants fee from Eisai and UCB. Douglas Nordli is
funded from NIH (1-RO1-NS43209) and CURE. He is an Associate Edi-
tor for UpToDate. Emilio Perucca has received speakers or consultancy
fees and/or research grants from the following pharmaceutical compa-
nies: Eisai, Biopharm Solutions, GW Pharma, Mylan, Sanofi, SK Life
Sciences, Sun Pharma, Takeda, and UCB Pharma. Torbjorn Tomson has
received research grants and/or speakers honoraria to his institution from
the following pharmaceutical companies: Eisai, GlaxoSmithKline, Novar-
tis, Bial, and UCB. He has also received research grants from CURE,
Stockholm County Council, and EU (DG Sante). Samuel Wiebe has
received speakers or consultancy fees and/or research/educational grants
from UCB, Electrocore, and Sunovion. Sameer Zuberi has received
research support and or speaker honoraria/consultancy fees from
Epilepsy Research UK, Dravet Syndrome UK, UCB Pharma, Yorkhill
Childrens Charity, GW Pharma, Brabant Pharma, and Zogenix. He is
Editor-in-Chief of the European Journal of Paediatric Neurology. We
confirm that we have read the Journals position on issues involved in
ethical publication and affirm that this report is consistent with those
guidelines.
Epilepsia, 58(4):512521, 2017
doi: 10.1111/epi.13709
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